The STAT3-Regulated Autophagy Pathway in Glioblastoma.
The STAT3-Regulated Autophagy Pathway in Glioblastoma.
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DOI：
10.3390/ph16050671
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发表时间：
2023-04-29
期刊：
影响因子：
--
通讯作者：
Pfeffer LM
中科院分区：
文献类型：
--
作者：
Laribee RN;Boucher AB;Madireddy S;Pfeffer LM
胶质母细胞瘤（GBM）是成人中最常见的原发性脑恶性肿瘤，预后不良。尽管基因组分析和手术技术的进步以及靶向治疗的发展，但大多数治疗方案是无效的，主要是姑息性的。自噬是细胞自我消化的一种形式，其目的是回收细胞内组分以维持细胞代谢。在这里，我们描述了一些最近的研究结果，表明GBM肿瘤对过度激活的自噬更敏感，导致自噬依赖性细胞死亡。GBM癌症干细胞（GSC）是GBM肿瘤群体的一个子集，其在肿瘤形成和进展、转移和复发中起关键作用，并且它们固有地对大多数治疗策略具有抗性。有证据表明，GSC能够适应缺氧、酸中毒和缺乏营养的肿瘤微环境。这些发现表明，自噬可能促进和维持GSC的干细胞样状态以及它们对癌症治疗的抵抗力。然而，自噬是一把双刃剑，在一定条件下可能具有抗肿瘤特性。还描述了STAT3转录因子在自噬中的作用。这些发现为未来的研究提供了基础，旨在靶向自噬依赖性途径，以克服GBM的固有治疗抗性，并通过自噬调节特异性靶向高度治疗抗性的GSC群体。
Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.
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影响因子：
4.8
作者：
Chang, Qing;Bournazou, Eirini;Bromberg, Jacqueline
通讯作者：
Bromberg, Jacqueline
影响因子：
45.3
作者：
Chakravarti, A;Zhai, G;Loeffler, JS
通讯作者：
Loeffler, JS
影响因子：
11.5
作者：
Cohen, MH;Johnson, JR;Pazdur, R
通讯作者：
Pazdur, R
DOI：
10.1016/j.bbrc.2017.07.098
发表时间：
2017-09-16
影响因子：
3.1
作者：
Du, Ziyun;Cai, Chun;Pfeffer, Lawrence M.
通讯作者：
Pfeffer, Lawrence M.
影响因子：
--
作者：
Tini P;Belmonte G;Toscano M;Miracco C;Palumbo S;Pastina P;Battaglia G;Nardone V;Butorano MA;Masucci A;Cerase A;Pirtoli L
通讯作者：
Pirtoli L